The physicochemical properties of a nanocarrier are essential parameters in drug delivery system design (DDS). This work addresses how G4.0 and G5.5 PAMAM dendrimers form complexes with bovine serum albumin (BSA) and fibrinogen (Fib). Analytical techniques, such as UV-vis spectrophotometry, dynamic light scattering (DLS), electrophoretic mobility, quartz crystal microbalance with dissipation monitoring (QCM-D), circular dichroism (CD), and contact angle were used to analyze the properties of the dendrimers-protein systems. The protein binding to dendrimers can alter the dendrimer's structure, mobility, conformation, and functional activity. Measurements of electrophoretic mobility allow tracking changes during the formation of dendrimer-protein complexes depending on environmental conditions. The compensation of functional groups charge in the dendrimer molecule by protein immobilization affects the complexes' effective charge. The results show that proteins' interactions with G4.0 and G5.5 dendrimer carriers are driven both by electrostatic and hydrophobic forces. The protein corona formed on the carrier's surface is very stable, as evidenced by the QCM-D measurements. On the other hand, the CD spectra indicate a change in the secondary structure of the protein. The size of the change is highly dependent on the protein to dendrimer ratio. Molecular dynamics (MD) clearly shows that the heterogeneous charge distribution on the surface of proteins plays an essential role in their behavior in the context of dendrimer systems. It enables identifying crucial amino acids involved in the formation of the dendrimer-protein complex and the observation of conformational changes in the system, and the participation of hydrophobic forces in this process.<br/>Protein corona formation on the carrier surface is advantageous for the potential use of DDS as it inhibits the adsorption of plasma proteins to the dendrimer surface, reduces dendrimer toxicity, and prevents rapid clearance from the blood, increasing circulation time.

Structure and function of protein corona on the dendrimer surface

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.